γδ T cells play a protective role during infection with Nippostrongylus brasiliensis by promoting goblet cell function in the small intestine

Summary The intestinal epithelium is rich in γδ T cells and the gut is a site of residence for a wide variety of pathogens, including nematodes. Although CD4 + T‐cell receptor (TCR) ‐αβ + T helper type 2 T cells are essential for the expulsion of intestinal nematodes, little information is available on the function of γδ T cells in this type of infection. Here, we demonstrate two major functions of γδ T cells as a potently protective T‐cell population against Nippostrongylus brasiliensis infection using γδ T‐cell‐deficient (TCR‐δ −/− ) mice. First, γδ T cells are required to initiate rapid expulsion of adult worms from the intestine and to limit egg production. Second, γδ T cells prevent the pathological intestinal damage associated with nematode infection, evident by increased clinical disease and more severe microscopic lesions in infected TCR‐δ −/− mice. γδ T‐cell deficiency led to delayed goblet cell hyperplasia in association with reduced expression of phosphorylated STAT6, MUC2, Trefoil factor‐3 (TFF3) and T helper type 2 cytokines including interleukin‐13 (IL‐13). TCR‐δ −/− mice also produced more interferon‐γ than wild‐type mice. Within the intraepithelial lymphocyte compartment, γδ T cells produced IL‐13. Adoptive transfer of γδ T cells or administration of recombinant IL‐13 to TCR‐δ −/− mice successfully reduced the egg production by N. brasiliensis . Collectively, these data provide strong evidence that γδ T cells play an important role in controlling infection with intestinal nematodes and limiting infection‐induced pathology.